Characterization of Inflammatory (Lymphoepithelioma-like) Hepatocellular Carcinoma: A Study of 8 Cases

Abstract

Context.-The World Health Organization has recently recognized lymphoepithelioma-like carcinoma, or inflammatory hepatocellular carcinoma, as a variant of hepatocellular carcinoma.Objective.-To identify and characterize the inflammatory hepatocellular carcinomas in our institution from 1988 to the present.Design.-All cases of hepatocellular carcinoma in our institution from 1988 to the present were reviewed and reclassified as lymphoepithelioma-like carcinoma and were studied in comparison to appropriately matched controls.Results.-Among the 8 cases of lymphoepithelioma-like carcinoma identified, the male to female ratio was 1:3, the mean age was 68.5 years (range, 57-78 years), and all of the cases were seen in noncirrhotic livers. The average numbers of lymphocytes were significantly higher in the cases than in the controls. T cells were predominant, with a uniform distribution of CD4 and CD8 positive cells. Cholangiolar differentiation was seen by K19 positivity as focal in 1 case and diffuse in 2 cases. In situ hybridization for Epstein-Barr virus was negative in all of the cases. Diffuse overexpression of p16 (.75% of cells) was seen in 2 cases, both of which were negative for the presence of transcriptionally active human papilloma virus by in situ hybridization. In our series, 3 of 8 cases (37.5%) showed local recurrence, which was similar to the controls (6 of 18; 33%), P . .99. Although the rate of distant metastases was lower among the cases (12.5%) than the controls (22.2%), the difference was not statistically significant (P . .99).Conclusion.-We present the first series of 8 cases of lymphoepithelioma-like carcinoma of the liver occurring in patients without cirrhosis and with a female preponderance and the absence of Epstein-Barr virus. Although clinical outcomes were similar to those of controls in our small series, additional data may be required for confirmation.

Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features

“…Interestingly, they were particularly frequent in the so‐called lymphoepithelioma‐like subtype of HCC. This uncommon histological variant, the pathogenesis of which is unknown, is characterized by sheets of neoplastic cells intermingled with a dense inflammatory stroma . Immunohistochemical studies have shown that this stroma is mainly made of cytotoxic T cells .…”

“…This uncommon histological variant, the pathogenesis of which is unknown, is characterized by sheets of neoplastic cells intermingled with a dense inflammatory stroma. (17,27) Immunohistochemical studies have shown that this stroma is mainly made of cytotoxic T cells. (28,29) Unlike other lymphoepithelioma-like carcinomas arising in other organs, no link with Epstein-Barr virus infection has been established.…”

Hepatocellular Carcinoma

“…Immunostains are typically needed to confi rm hepatocellular differentiation; a panel of immunostains for glypican-3, HepPar1, and arginase-1 can be helpful. The reactive lymphocytes are primarily T cells [ 96 ]. Also of note, the epithelial component in lymphoepithelioma-like cholangiocarcinoma is typically EBV positive, while the epithelial component in both lymphoepithelioma-like hepatocellular carcinoma and in lymphocyterich hepatocellular carcinoma is EBV negative [ 92 , 95 , 96 ], with the exception of one case report [ 97 ].…”

An update on the histological subtypes of hepatocellular carcinoma

“…Previously known as lymphoepithelioma-like HCC, lymphocyte-rich HCC is characterized by an immune-rich stroma [19,20] . Wada et al [21] defined this subtype by the presence of more than 100 tumorinfiltrating lymphocytes in 10 high-power fields.…”